Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization

The increasing prevalence of antibiotic-resistant bacteria is a global threat to public health. Agricultural use of antibiotics is believed to contribute to the spread of antibiotic resistance, but the mechanisms by which many agricultural practices influence resistance remain obscure. Although manure from dairy farms is a common soil amendment in crop production, its impact on the soil microbiome and resistome is not known. To gain insight into this impact, we cultured bacteria from soil before and at 10 time points after application of manure from cows that had not received antibiotic treatment. Soil treated with manure contained a higher abundance of β-lactam–resistant bacteria than soil treated with inorganic fertilizer. Functional metagenomics identified β-lactam–resistance genes in treated and untreated soil, and indicated that the higher frequency of resistant bacteria in manure-amended soil was attributable to enrichment of resident soil bacteria that harbor β-lactamases. Quantitative PCR indicated that manure treatment enriched the bla_CEP-04 gene, which is highly similar (96%) to a gene found previously in a Pseudomonas sp. Analysis of 16S rRNA genes indicated that the abundance of Pseudomonas spp. increased in manure-amended soil. Populations of other soil bacteria that commonly harbor β-lactamases, including Janthinobacterium sp. and Psychrobacter pulmonis, also increased in response to manure treatment. These results indicate that manure amendment induced a bloom of certain antibiotic-resistant bacteria in soil that was independent of antibiotic exposure of the cows from which the manure was derived. Our data illustrate the unintended consequences that can result from agricultural practices, and demonstrate the need for empirical analysis of the agroecosystem.Agriculture affects human health through both the consumption and production of food for the human diet. Manure from pig and cattle farms is commonly used as a substitute for inorganic nitrogen and phosphorus fertilizers for agricultural crops worldwide, especially in organic farming practices (1–6). With the increasing consumer demand for organically produced food, the use of animal manure, which conforms to organic conventions, will likely increase in the future. According to the National Organic Program, raw manure may be used up to 90–120 d before harvest, depending on the crop, and composted manure may be applied at any time. There are no restrictions on the source of manure (1).Animal manure is an important reservoir of antibiotic-resistant bacteria, antibiotic-resistance genes (collectively known as the “resistome”), and pathogens (2, 7–12). Although antibiotic use increases antibiotic-resistance genes and resistant bacteria in manure (13–16), antibiotic-resistant bacteria are also abundant in manure from animals with no history of antibiotic treatment, indicating the natural presence of bacteria intrinsically resistant to antibiotics in animal gastrointestinal tracts (2, 17, 18).There is increasing concern about the use of manure as an agricultural amendment because of its possible contribution to the pool of resistance genes to resident soil bacteria and pathogens (2, 19). Antibiotic-resistance genes from the soil resistome can enter the food chain via contaminated crops or groundwater (5, 20), and have potential consequences for human health if transferred to human pathogens. Studies assessing the impact of fertilization with pig manure on the soil resistome have shown that excessive application of manure from farms with intensive sulfonamide use can lead to an increase of antibiotic-resistance genes in soil (2, 3); however, most studies have found that such increases are transient when the manure is applied at recommended rates (2, 21, 22). Cow manure from dairy farms, which use β-lactam antibiotics predominantly to prevent and treat diseases (23), is commonly used in crop production, but its impact on the soil resistome has yet to be investigated.Along with its impact on the soil resistome, the application of manure can affect the composition and functional properties of soil microbial communities, as has been demonstrated by community fingerprinting (21, 24). Recent advances in DNA-based analysis, such as metagenomics and quantitative PCR (qPCR), offer greater precision in such studies, enabling identification of affected community members (25) and their resistance genes (4).In the present study, we assessed the impact of cow manure on the composition and resistance profiles of bacterial communities in soil. Our results show that manure from cows that had not been treated with antibiotics increased the populations of resident soil bacteria harboring genes for resistance to β-lactam antibiotics, whereas inorganic fertilizers did not. These results demonstrate the complexity, and at times nonintuitive consequences, of agricultural practices.     

Identification of prognostic markers in diffuse midline gliomas H3K27M‐mutant

Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M‐mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M‐mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M‐mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c‐MET and p53), next‐generation sequencing and comparative genomic hybridization array. Forty‐nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M‐mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M‐mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity.     

The Ontogeny of Masticatory Muscle Architecture in Microcebus murinus

The masticatory apparatus has been the focus of many studies in comparative anatomy—especially analyses of skulls and teeth, but also of the mandibular adductor muscles which are responsible for the production of bite force and the movements of the mandible during food processing and transport. The fiber architecture of these muscles has been correlated to specific diets (e.g., prey size in felids) and modes of foraging (e.g., tree gouging in marmosets). Despite the well-elucidated functional implications of this architecture, little is known about its ontogeny. To characterize age-related myological changes, we studied the masticatory muscles in a large (n = 33) intraspecific sample of a small, Malagasy primate, Microcebus murinus including neonatal through geriatric individuals. We removed each of the mandibular adductors and recorded its mass as well as other linear measurements. We then chemically dissected each muscle to study its architecture—fascicle length and physiological cross-sectional area (PCSA) which relate to stretch (gape) and force capabilities, respectively. We observed PCSA and muscle mass to increase rapidly and plateau in adulthood through senescence. Fascicle lengths remained relatively constant once maximal length was reached, which occurred early in life, suggesting that subsequent changes in PCSA are driven by changes in muscle mass. Quadratic curvilinear models of each of the architectural variables of all adductors combined as well as individual muscles regressed against age were all significant. Anat Rec, 303:1364–1373, 2020. © 2019 American Association for Anatomy     

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: A french multicenter study

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9 years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5 years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36 months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6 mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.     

Nicotinic Acetylcholine Receptor Density in the “Higher-Order” Thalamus Projecting to the Prefrontal Cortex in Humans: a PET Study

Molecular Imaging and Biology - The parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between...     

p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma

The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric carcinomas from a low incidence population. Formalin-fixed, paraffin-embedded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mutation by single-strand conformation polymorphism analysis of exons 5-8. Nuclear p53 accumulation was detected in 23% of tumours and mutation in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lymph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of invasion, grade and histological type showed no significant associations with either p53 alteration. In univariate analysis, both alterations were associated with significantly shortened patient survival. The 5-year survival rate for patients with a p53 mutation was 9% compared to 42% for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma. © 1996 Wiley-Liss, Inc.     

Early commercial experience with a newly designed balloon-expandable transcatheter heart valve: 30-day outcomes and implications of preprocedural computed tomography

OBJECTIVESWe herein report a single-centre experience with the SAPIEN 3 Ultra balloon-expandable transcatheter aortic valve implantation (TAVI) system.METHODSBetween March 2019 and January 2020, a total of 79 consecutive patients received transfemoral TAVI using the SAPIEN 3 Ultra device. Data were retrospectively analysed according to updated Valve Academic Research Consortium-2 definitions. Detailed analysis of multislice computed tomography data was conducted to identify potential predictors for permanent pacemaker (PPM) implantation and residual paravalvular leakage (PVL) post TAVI.Open in a separate windowGraphical AbstractRESULTSDevice success and early safety were 97.5% (77/79) and 94.9% (75/79) with resulting transvalvular peak/mean pressure gradients of 21.1 ± 8.2/10.9 ± 4.4 and PVL >mild in 0/79 patients (0%). Mild PVL was seen in 18.9% (15/79) of cases. Thirty-day mortality was 2.5% (2/79). The Valve Academic Research Consortium-2 adjudicated clinical end points disabling stroke, acute kidney injury and myocardial infarction occurred in 1.3% (1/79), 5.1% (4/79) and 0% (0/79) of patients. Postprocedural PPM implantation was necessary in 7.6% (6/79) of patients. Multislice computed tomography analysis revealed significantly higher calcium amounts of the right coronary cusp in patients in need for postprocedural PPM implantation and a higher eccentricity index in patients with postinterventional mild PVL.CONCLUSIONSFirst experience with this newly designed balloon-expandable-transcatheter heart valve demonstrates adequate 30-day outcomes and haemodynamic results with low mortality, low rates of PPM implantation and no residual PVL >mild. The herein-presented multislice computed tomography values with an elevated risk for PPM implantation and residual mild PVL may help to further improve outcomes with this particular transcatheter heart valve in TAVI procedures.     

Profound bilateral deafness complicating aortic arch surgery

Hearing loss is a rare complication of cardiac surgery; bilateral profound deafness has never been reported in this setting. A 45-year-old male presented with profound bilateral sudden deafness following arch surgery and frozen elephant trunk. Patient’s presentation, surgery details and aetiological mechanisms are discussed.     

Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population,Normandy, France,November to December 2021

Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.